The non-canonical role of Atg family members as suppressors of innate antiviral immune signaling.

Recent research on autophagy clearly demonstrates that the autophagosome-lysosome pathway plays essential roles in elimination of certain pathogens such as group A Streptococcus, Mycobacterium tuberculosis, Listeria monocytogenes, and herpesvirus. (1-4) We have recently found that a key regulator of the autophagic process, the Atg12-Atg5 conjugate, associates with the signaling molecules retinoic acid-inducible gene I (RIG-I) and interferon-beta promoter stimulator 1 (IPS-1), which are essential for recognition of RNA virus infection and which transmit signals to upregulate type I interferons (IFNs). Interestingly, the Atg12-Atg5 conjugate seemed to negatively regulate the type I IFN modulating pathway through direct interaction with caspase recruitment domains (CARDs) presented by RIG-1 and IPS-1.(5) Thus, in contrast to the bactericidal properties of autophagic processes, the autophagy regulator (the Atg12-Atg5 conjugate) appeared to promote RNA virus replication by inhibiting innate anti-virus immune responses. In this addendum, we discuss the non-canonical role of the Atg12-Atg5 conjugate as a suppressor of innate immune responses.